mitomycin G | 74148-46-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: mitomycin G
• 英文别名: (4S,6S,7R)-11-amino-7-methoxy-5,12-dimethyl-8-methylidene-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-diene-10,13-dione
• CAS: 74148-46-2
• 化学式: C₁₅H₁₇N₃O₃
• 分子量: 287.318
• InChiKey: FEJAPZGDIFMDMP-HTKKXEBZSA-N

物化性质

• 熔点：
  238-241 °C (decomp)
• 沸点：
  454.3±45.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  10-Des(carbamoyloxy)-10-iodoporfiromycin 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以47%的产率得到mitomycin G
  参考文献：
  名称：

  C(10) Halogen 10-Des(carbamoyloxy)porfiromycins: Synthesis, Chemistry, and Biological Activity

  摘要：

  An efficient four-step procedure for the preparation of C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 beginning with mitomycin C(1) is described. Solvolytic removal (NaOMe, MeOH/benzene) of the C(10) carbamoyl group in 1 followed by N-methylation (dimethyl sulfate (15 equiv), 1,8-bis(dimethylamino)naphthalene (15 equiv) in THF) provided 10-decarbamoylporfiromycin (7) in 65% yield. Treatment of 7 with methanesulfonyl chloride in pyridine gave 10-decarbamoyl-10-methanesulfonylporfiromycin (8) in 83% yield, which upon heating with metal halides (i.e., LiCl, LiBr, NaI) in either DMF or ethylene glycol dimethyl ether furnished the C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 in 68-81% yields. The C(10) halogen 10-des(carbamoyloxy)porfiromycins served as useful starting materials for C(10)-modified derivatives. Treatment of the C(10) bromo derivative 4 with 1,8-diazabicyclo[5.4.0]undec-7-ene provided the elimination product, 10-des(carbamoyloxy)-9-dehydroporfiromycin (12), while addition of AgSCN to the C(10) iodo porfiromycin 5 led to the substituted adducts 10-des(carbamoyloxy)-10-thiocyanatoporfiromycin (10) and 10-des(carbamoyloxy)-10-thiocyanato-9-epi-mitomycin D (11). The C(10) halogen 10-des(carbamoyloxy)porfiromycins also underwent novel radical and thermal skeletal rearrangements. Treatment of the C(10) iodo derivative 5 with tributyltin hydride and AIBN led to the production of the ring-expanded quinone 14. Thermolysis of the C(10) bromo (4) and the C(10) iodo (5) adducts gave the tetracycles 18 and 19, respectively, in which the C(2) nitrogen bond in the starting porfiromycin had been preferentially cleaved in favor of the C(1) bond. Potential pathways for these rearrangements are briefly outlined. The in vitro cytotoxicities of 3-5 in human colon carcinoma cell lines were evaluated. All three C(10) halogen 10-des(carbamoyloxy)porfiromycins were noticeably less potent than mitomycin C.

  DOI：

  10.1021/jo00116a024

文献信息

• Kono, Motomichi; Kasai, Masaji; Shirahata, Kunikatsu, Synthetic Communications, 1989, vol. 19, # 11-12, p. 2041 - 2048
  作者：Kono, Motomichi、Kasai, Masaji、Shirahata, Kunikatsu

  DOI：——

  日期：——
• C(10) Halogen 10-Des(carbamoyloxy)porfiromycins: Synthesis, Chemistry, and Biological Activity
  作者：Daeock Choi、Byungwoo Yoo、Kimberly L. Colson、Gary E. Martin、Harold Kohn

  DOI：10.1021/jo00116a024

  日期：1995.6

  An efficient four-step procedure for the preparation of C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 beginning with mitomycin C(1) is described. Solvolytic removal (NaOMe, MeOH/benzene) of the C(10) carbamoyl group in 1 followed by N-methylation (dimethyl sulfate (15 equiv), 1,8-bis(dimethylamino)naphthalene (15 equiv) in THF) provided 10-decarbamoylporfiromycin (7) in 65% yield. Treatment of 7 with methanesulfonyl chloride in pyridine gave 10-decarbamoyl-10-methanesulfonylporfiromycin (8) in 83% yield, which upon heating with metal halides (i.e., LiCl, LiBr, NaI) in either DMF or ethylene glycol dimethyl ether furnished the C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 in 68-81% yields. The C(10) halogen 10-des(carbamoyloxy)porfiromycins served as useful starting materials for C(10)-modified derivatives. Treatment of the C(10) bromo derivative 4 with 1,8-diazabicyclo[5.4.0]undec-7-ene provided the elimination product, 10-des(carbamoyloxy)-9-dehydroporfiromycin (12), while addition of AgSCN to the C(10) iodo porfiromycin 5 led to the substituted adducts 10-des(carbamoyloxy)-10-thiocyanatoporfiromycin (10) and 10-des(carbamoyloxy)-10-thiocyanato-9-epi-mitomycin D (11). The C(10) halogen 10-des(carbamoyloxy)porfiromycins also underwent novel radical and thermal skeletal rearrangements. Treatment of the C(10) iodo derivative 5 with tributyltin hydride and AIBN led to the production of the ring-expanded quinone 14. Thermolysis of the C(10) bromo (4) and the C(10) iodo (5) adducts gave the tetracycles 18 and 19, respectively, in which the C(2) nitrogen bond in the starting porfiromycin had been preferentially cleaved in favor of the C(1) bond. Potential pathways for these rearrangements are briefly outlined. The in vitro cytotoxicities of 3-5 in human colon carcinoma cell lines were evaluated. All three C(10) halogen 10-des(carbamoyloxy)porfiromycins were noticeably less potent than mitomycin C.